Identification of 4-Oxo-2-hexenal and Other Direct Mutagens Formed in Model Lipid Peroxidation Reactions as dGuo Adducts
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- 作者：Muneyuki Maekawa ; Kazuaki Kawai ; Yoshikazu Takahashi ; Hikaru Nakamura ; Takumi Watanabe ; Ryuichi Sawa ; Kenji Hachisuka ; and Hiroshi Kasai
- 刊名：Chemical Research in Toxicology
- 出版年：2006
- 出版时间：January 2006
- 年：2006
- 卷：19
- 期：1
- 页码：130 - 138
- 全文大小：163K
- 年卷期：v.19,no.1(January 2006)
- ISSN：1520-5010
文摘
We searched for mutagens that react with 2'-deoxyguanosine (dGuo) in model systems of lipidperoxidation. To autoxidation systems of methyl linoleate (model of 
-6 fat), methyl 
-linolenate (MLN)(model of -3 fat), and commercial salad oil, dGuo was added. The reaction mixtures were analyzed byHPLC. Six adducts were detected, and their structures were determined by 1H and 13C NMR, UV, andmass spectra and by comparison with synthetic authentic samples. The mutagens that reacted with dGuoto form these adducts were proposed as glyoxal, glyoxylic acid, ethylglyoxal, and 4-oxo-2-hexenal (4-OHE). The formation of 8-hydroxy-dGuo, an oxidized product of dGuo, was also detected in the modelreaction mixtures. Among them, glyoxal and glyoxylic acid are known mutagens, while ethylglyoxaland 4-OHE, produced from MLN, have not been reported as mutagens thus far. We confirmed themutagenic activity of 4-OHE with Salmonella strains, TA100 and TA104, without S9 mix. Thesecompounds may be involved in lipid peroxide-related cancers.
-6 fat), methyl -linolenate (MLN)(model of -3 fat), and commercial salad oil, dGuo was added. The reaction mixtures were analyzed byHPLC. Six adducts were detected, and their structures were determined by 1H and 13C NMR, UV, andmass spectra and by comparison with synthetic authentic samples. The mutagens that reacted with dGuoto form these adducts were proposed as glyoxal, glyoxylic acid, ethylglyoxal, and 4-oxo-2-hexenal (4-OHE). The formation of 8-hydroxy-dGuo, an oxidized product of dGuo, was also detected in the modelreaction mixtures. Among them, glyoxal and glyoxylic acid are known mutagens, while ethylglyoxaland 4-OHE, produced from MLN, have not been reported as mutagens thus far. We confirmed themutagenic activity of 4-OHE with Salmonella strains, TA100 and TA104, without S9 mix. Thesecompounds may be involved in lipid peroxide-related cancers.